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101.
Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice. 相似文献
102.
Balachandran VP Cavnar MJ Zeng S Bamboat ZM Ocuin LM Obaid H Sorenson EC Popow R Ariyan C Rossi F Besmer P Guo T Antonescu CR Taguchi T Yuan J Wolchok JD Allison JP DeMatteo RP 《Nature medicine》2011,17(9):1094-1100
Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal tumor (GIST) and produces a clinical response in 80% of patients. The mechanism is believed to depend predominantly on the inhibition of KIT-driven signals for tumor-cell survival and proliferation. Using a mouse model of spontaneous GIST, we found that the immune system contributes substantially to the antitumor effects of imatinib. Imatinib therapy activated CD8(+) T cells and induced regulatory T cell (T(reg) cell) apoptosis within the tumor by reducing tumor-cell expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido). Concurrent immunotherapy augmented the efficacy of imatinib in mouse GIST. In freshly obtained human GIST specimens, the T cell profile correlated with imatinib sensitivity and IDO expression. Thus, T cells are crucial to the antitumor effects of imatinib in GIST, and concomitant immunotherapy may further improve outcomes in human cancers treated with targeted agents. 相似文献
103.
Los FC Kao CY Smitham J McDonald KL Ha C Peixoto CA Aroian RV 《Cell host & microbe》2011,10(2):147-157
Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed the clinically important HVR-containing M proteins of the human pathogen Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost exclusively against the C-terminal part and not against the N-terminal HVR. Similar results were obtained for mice and humans with invasive S.?pyogenes infection. Nevertheless, only anti-HVR antibodies protected efficiently against infection, as shown by passive immunizations. The HVR fused to an unrelated protein elicited no antibodies, implying that it is inherently weakly immunogenic. These data indicate that the M protein HVR evades antibody attack not only through antigenic variation but also by weak immunogenicity, a paradoxical observation that may apply to other HVR-containing proteins. 相似文献
104.
105.
106.
Ferdinand Bohlmann Thomas Gerke Jasmin Jakupovic Robert M. King Harold Robinson 《Phytochemistry》1984,23(5):1183-1184
Viguiera oblongifolia afforded two known furanoheliangolides and a new cadinane derivative whose structure was established by spectroscopic methods. From V. lanceolata 17,18-dihydrobudlein A was isolated. 相似文献
107.
108.
Ferdinand Bohlmann Christa Zdero Robert M. King Harold Robinson 《Phytochemistry》1984,23(7):1509-1511
A reinvestigation of the aerial parts of Conocliniopsis prasiifolia afforded two furoheliangolides, conoprasiolide-9-O,5′-O-diacetate and 相似文献
109.
Ferdinand Bohlmann Kazuyasu Umemoto Jasmin Jakupovic Robert M. King Harold Robinson 《Phytochemistry》1984,23(8):1669-1672
The investigation of two Ferreyanthus species afforded seven germacranolides which have not been isolated previously. Two derivatives of linalol were also present. The structures were elucidated by spectroscopic methods. Chemotaxonomic relationships are briefly discussed. 相似文献
110.
Nezhun Gören Ayhan Ulubelen Jasmin Jakupovic Ferdinand Bohlmann Michael Grenz 《Phytochemistry》1984,23(10):2281-2284
In addition to known compounds an investigation of the fruits of Smyrnium rotundifolium afforded four new germacrane derivatives, all closely related to glechomanolide, one being a secogermacrane anhydride. The new compounds were 8,9-epoxy-8,9-secoglechomanolide, 1β,10α-epoxy-4-methoxy-8-hydroxyglechomanolide and 8-oxo-8,9-secoglechomanolide. The structures were assigned by spectral methods as well as by some chemical reactions. 相似文献